中文摘要
根据中医以方测证原理,脊髓胶质细胞活化介导的神经性炎症(神经病理性疼痛 [NP]重要发病机制)可归属于蒙医寒性“协日乌素”病范畴,这也在那如-3治疗坐骨神经痛的显著疗效中得到验证。但其药效机制不明。我们前期研究发现那如-3慢性给药对NP小鼠痛敏阈值有累加效应并与脊髓阳性胶质细胞数目降低相关,因此提出“那如-3存在对胶质细胞活化抑制,进而驱除脊髓‘协日乌素’达到缓解中枢敏化的镇痛机制”假说。项目拟采用经典脊神经结扎模型观察那如-3对NP小鼠机械、热痛敏的影响;IHC筛选药效靶细胞;AimPlex流式高通量多因子检测技术筛选药效相关因子;并配合体外胶质细胞、神经元培养及共培养方法,通过电生理检测、激光共聚焦、WB、PCR等技术多方面探索那如-3对胶质细胞功能调控的途径、环节、靶点;相关研究结果将有助于阐释蒙药那如-3治疗NP的多靶向作用机制,对指导民族药的临床合理用药及进一步研发也具重要意义。
英文摘要
According to TCM syndrome square measuring principle, the important pathogenesis of neuropathic pain (NP): spinal glial cell activation-driven neuroinflammation, could be attributable to cold “Xie-Ri-Wu-Su” disease category in Mongolian Medicine, which was also verified by the remarkable effect of Mongolian Medicine Naru-3 (NR-3) in clinical treatment of sciatica et al., but the mechanisms remain to be clear. Our previous study found that mouse hyperalgesia thresholds had a cumulative effect and were associated with the reduction of spinal positive glial cells by NR-3 chronic administration in NP model, so we hypothesized that “It is the suppression of glial cell activation in the spinal cord, which caused by chronic administration of NR-3, and the subsequent dispersion of ‘Xie-Ri-Wu-Su’ that lead to the alleviation of central sensitization in NP mouse”. Thus, our project intends to adopt the classic L5 spinal nerve ligation model to observe thermal and mechanical hyperalgesia to clarify the pharmacodynamics of NR-3 on NP mice; and screen the efficacy of target cells by ICH and AimPlex Multiple Immunoassays for Flow; by using glial cells or neurons cultures, glial-glial cells or glial-neurons co-cultures in vitro, and in line with westernblotting, electrophysiological testing, confocal laser scanning techniques to explore the approach, links and targets of NR-3 on the regulation of glial cells. Our results will help explain the multi-targeted mechanisms of NR-3 on NP treatment, guide rational NR-3 use in clinic, and further, for the development of new ethnic medicine, which possesses important significance for NP study and treatment.
